Extracorporeal photochemotherapy in secondary clinical non-responsiveness to netakimab in psoriasis patients: case reports.

Psoriasis is one of the most common and socially significant dermatological diseases. For a long time, the main treatment approach consisted of a combination of topical agents, physiotherapeutic methods, and systemic medications that influence keratinocyte proliferation. Currently, due to advances in understanding the immunopathogenesis of psoriasis, the most evidence-based approach is the use of gene-engineered biological therapy (GEBT). The introduction of this new class of drugs has significantly improved the efficacy and safety of treatment for moderate to severe psoriasis. One of the notable drawbacks of GEBT is the predictable development of secondary clinical therapy failure over prolonged use. Traditionally, this phenomenon was mainly attributed to the formation of anti-drug antibodies (ADA) against the targeted agents. However, accumulating clinical data increasingly report cases where a "loss of response" occurs despite the absence of ADA. This situation has prompted active investigation into other potential mechanisms underlying secondary clinical inefficacy, including the activation of alternative immunopathological pathways in psoriasis. To address secondary clinical failure of GEBT, several approaches are currently utilized: addition of adjuvant therapy (most commonly methotrexate), switching to a different target drug, or reinitiating treatment with the same gene-engineered biological agent. This article explores the possibility of applying extracorporeal photochemotherapy (ECP) in cases of secondary clinical inefficacy of netakimab, specifically when no anti-drug antibodies are present. The presented clinical cases demonstrate good therapeutic outcomes of this method. The discussion includes potential mechanisms underlying the development of secondary clinical inefficacy and provides a pathogenetically grounded rationale for using ECP as a comprehensive immunomodulatory method inducing lymphocyte apoptosis, modulating antigen-presenting cell functions, promoting T-regulatory cell induction, and altering cytokine profiles. Overall, this method supports the restoration of immune homeostasis, which may lead to reversal of the pathological immune processes induced by GEBT, restoring the immune response to the initial inflammatory mechanisms characteristic of psoriasis.